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Paranodal lesions in chronic inflammatory demyelinating polyneuropathy associated with anti-Neurofascin 155 antibodies. | LitMetric

AI Article Synopsis

  • Antibodies to Contactin-1 and Neurofascin 155 (Nfasc155) have been linked to chronic inflammatory demyelinating polyneuropathy (CIDP), affecting patients' nerve function.
  • A study using electron microscopy showed that patients with anti-Nfasc155 antibodies had a loss of important junctions in their myelinated axons, which contributed to nerve conduction issues.
  • The research suggests that these antibodies disrupt the stability of junctions between nerve cells, potentially worsening the patients' symptoms and nerve damage.

Article Abstract

Antibodies to Contactin-1 and Neurofascin 155 (Nfasc155) have recently been associated with subsets of patients with chronic inflammatory demyelinating polyneuropathy (CIDP). Contactin-1 and Nfasc155 are cell adhesion molecules that constitute the septate-like junctions observed by electron microscopy in the paranodes of myelinated axons. Antibodies to Contactin-1 have been shown to affect the localization of paranodal proteins both in patient nerve biopsies and in animal models after passive transfer. However, it is unclear whether these antibodies alter the paranodal ultrastructure. We examined by electron microscopy sural nerve biopsies from two patients presenting with anti-Nfasc155 antibodies, and also four patients lacking antibodies, three normal controls, and five patients with other neuropathies. We found that patients with anti-Nfasc155 antibodies presented a selective loss of the septate-like junctions at all paranodes examined. Further, cellular processes penetrated into the expanded spaces between the paranodal myelin loops and the axolemma in these patients. These patients presented with important nerve conduction slowing and demyelination. Also, the reactivity of anti-Nfasc155 antibodies from these patients was abolished in neurofascin-deficient mice, confirming that the antibodies specifically target paranodal proteins. Our data indicate that anti-Nfasc155 destabilizes the paranodal axo-glial junctions and may participate in conduction deterioration.

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Source
http://dx.doi.org/10.1016/j.nmd.2016.10.008DOI Listing

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